Mechanism of the antidiuretic effect of saluretic drugs Studies in patients with diabetes insipidus In patients with diabetes insipidus who remained on a low salt diet, antidiuresis following the administration of saluretic drugs persisted long after the drugs were discontinued. Sodium repletion terminated the antidiuresis. The antidiuretic phenomenon occurred with mercurial diuretics, several thiazide derivatives, quinethazone, and ethacrynic acid. Antidiuresis was partially or totally inhibited by prevention of sodium or potassium losses during saluretic therapy. There was a significant correlation between antidiuresis and body fluid volume contraction. Urine was transiently concentrated by acute administration of vasopressin to a greater extent during polythiazide therapy than during a control period. This is taken as evidence that the medullary interstitium is more hypertonic after diuretic treatment. The observed antidiuresis appeared to be secondary to the contraction of body fluid volume. The renal mechanism for antidiuresis seems to be related to enhanced proximal sodium and water reabsorption in the renal tubules and to increased medullary hypertonicity, with a larger tubular clearance of free water. The formation of free water in the urine is an important phYSiological phenomenon, which is regulated by several control mechanisms and not ;ust by antidiuretic hormone activity. Guadalupe Ramos, Alfonso Rivera,* Jose Carlos Pena, and Federico Dies Mexico City, Mexico Departamento de Fisiologia Clinica, Instituto Nacional de la Nutrici6n The administration of thiazide deriva tives to patients 8 or nonnal subjects 6 under going water diuresis increases sodium and potassium excretion, but decreases urine flow and free water clearance. This anti diuretic effect has been ascribed to a de pression of free water fonnation,17 to a decrease in glomerular filtration rate,14 to an inhibition of aldosterone action on the distal tubule,16 to increased water perme ability of the collecting ducts,4, 6 or to in creased proximal sodium reabsorption re sulting from salt depletion. 3 , 11 Received for publication Dec. 21, 1967. "Deceased. The experiments reported here were designed to detennine whether diuretic induced anti diuresis was due to a primary or to a secondary action of the drugs. The results indicate that the observed antidiu resis seems to be secondary to the con traction of body fluid volume caused by various diuretic agents. The renal mecha nism for the antidiuresis appears to be related to enhanced proximal sodium and water reabsorption in the renal tubules and to increased medullary hypertoniCity with a larger tubular clearance of free water. The latter finding may be related to de creased medullary blood flow. 557